chemotherapy in treating patients with myelodysplastic syndrome before donor stem cell transplant

Conditions: Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Myelodysplastic Syndrome; Secondary Myelodysplastic Syndrome

Summary: this randomized clinical trial studies different chemotherapies in treating patients with myelodysplastic syndrome before donor stem cell transplant. giving chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells, and may prevent the myelodysplastic syndrome from coming back after the transplant. when the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

outline: patients are randomized to 1 of 2 treatment arms. arm a: patients receive decitabine or azacitidine intravenously (iv) or subcutaneously (sc) for 7 days. treatment repeats every 28 days for 4 cycles of decitabine or 6 cycles of azacitidine in the absence of disease progression or unacceptable toxicity. arm b: patients receive induction-like chemotherapy per standard of care or per experimental protocol. this study does not require a specific chemotherapy regimen for arm b. after completion of study treatment, patients are followed up for 18 months.

Eligibility criteria:
inclusion criteria: * diagnosis of de novo or secondary myelodysplastic syndrome (mds), including chronic myelomonocytic leukemia, as defined by the 2008 world health organization classification system * patients must have measurable disease requiring cytoreduction, defined as a bone marrow myeloblast count \>= 5% and \< 20% on morphologic examination or by flow cytometry in cases in which adequate morphologic examination is not possible * patients must be considered to have an acceptable risk of early mortality with intensive chemotherapy as determined by the attending physician at the time of the initial visit; since the specific therapy within each arm will be determined after randomization, there is no threshold of organ dysfunction or performance status for inclusion * considered a potential transplant candidate; the attending/treating physician will determine transplant candidacy at the time of consent * capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent exclusion criteria: * a diagnosis of acute promyelocytic leukemia as defined by the 2008 world health organization classification system * previous treatment for mds or acute myeloblastic leukemia (aml) with intensive chemotherapy regimen (induction chemotherapy) or hypomethylating agent * have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment * patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) * females who are pregnant or breastfeeding * fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment * any uncontrolled or significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results * clinical evidence suggestive of central nervous system (cns) involvement with mds unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal fluid (csf)

Keywords: myelodysplastic syndrome chronic myelomonocytic leukemia bone marrow transplant hypomethylating agent induction chemotherapy